Ultrasensitive standoff chemical sensing based on nonlinear multi-photon laser wave-mixing spectroscopy

Nonlinear multi-photon laser wave mixing is presented as an ultrasensitive optical detection method for chem/bio agents in thin films and gas-and liquid-phase samples. Laser wave mixing is an unusually sensitive optical absorption-based detection method that offers significant inherent advantages including excellent sensitivity, small sample requirements, short optical path lengths, high spatial resolution, high spectral resolution and standoff remote detection capability. Wave mixing can detect trace amounts of chemicals even when using micrometer-thin samples, and hence, it can be conveniently interfaced to fibers, microarrays, microfluidic systems, lab-on-a-chip, capillary electrophoresis and other capillary-or fiber-based chemical separation systems. The wave-mixing signal is generated instantaneously as the two input laser beams intersect inside the analyte of interest. Laser excitation wavelengths can be tuned to detect multiple chemicals in their native form since wave mixing can detect both fluorescing and non-fluorescing samples at parts-per-trillion or better detection sensitivity levels. The wave-mixing signal is a laser-like coherent beam, and hence, it allows reliable and effective remote sensing of chemicals. Sensitive wave-mixing detectors offer many potential applications including sensitive detection of biomarkers, early detection of diseases, sensitive monitoring of environmental samples, and reliable detection of hazardous chem/bio agents with a standoff detection capability.